Abstract
The goal of this study was to determine which neural elements are excited by microstimulation of the central nervous system. A cable model of a neuron including an axon, initial segment, axon hillock, soma, and simplified dendritic tree was used to study excitation with an extracellular point source electrode. The model reproduced a wide range of experimentally documented extracellular excitation patterns. The site of action potential initiation (API) was a function of the electrode position, stimulus duration, and stimulus polarity. The axon or initial segment was always the site of API at threshold. When the electrode was positioned near the cell body, the site of excitation was dependent on the stimulus amplitude. With the electrode in close proximity to the neuron, short-duration cathodic pulses produced lower thresholds with the electrode positioned over the axon than over the cell body, and long-duration stimuli produced opposite relative thresholds. This result was robust to alterations in either the maximum conductances or the intracellular resistivities of the model. The site of maximum depolarization was not always an accurate predictor of the site of API, and the temporal evolution of the changes in membrane potential played a strong role in determining the site of excitation.
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Selected References
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- Barrett J. N., Crill W. E. Specific membrane properties of cat motoneurones. J Physiol. 1974 Jun;239(2):301–324. doi: 10.1113/jphysiol.1974.sp010570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BeMent S. L., Ranck J. B., Jr A model for electrical stimulation of central myelinated fibers with monopolar electrodes. Exp Neurol. 1969 Jun;24(2):171–186. doi: 10.1016/0014-4886(69)90013-2. [DOI] [PubMed] [Google Scholar]
- BeMent S. L., Ranck J. B., Jr A quantitative study of electrical stimulation of central myelinated fibers. Exp Neurol. 1969 Jun;24(2):147–170. doi: 10.1016/0014-4886(69)90012-0. [DOI] [PubMed] [Google Scholar]
- Clements J. D., Redman S. J. Cable properties of cat spinal motoneurones measured by combining voltage clamp, current clamp and intracellular staining. J Physiol. 1989 Feb;409:63–87. doi: 10.1113/jphysiol.1989.sp017485. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Colbert C. M., Johnston D. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons. J Neurosci. 1996 Nov 1;16(21):6676–6686. doi: 10.1523/JNEUROSCI.16-21-06676.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cullheim S., Fleshman J. W., Glenn L. L., Burke R. E. Membrane area and dendritic structure in type-identified triceps surae alpha motoneurons. J Comp Neurol. 1987 Jan 1;255(1):68–81. doi: 10.1002/cne.902550106. [DOI] [PubMed] [Google Scholar]
- Cullheim S., Kellerth J. O. A morphological study of the axons and recurrent axon collaterals of cat sciatic alpha-motoneurons after intracellular staining with horseradish peroxidase. J Comp Neurol. 1978 Apr 1;178(3):537–557. doi: 10.1002/cne.901780309. [DOI] [PubMed] [Google Scholar]
- Fabricius C., Berthold C. H., Rydmark M. Dimensions of individual alpha and gamma motor fibres in the ventral funiculus of the cat spinal cord. J Anat. 1994 Apr;184(Pt 2):319–333. [PMC free article] [PubMed] [Google Scholar]
- Fleshman J. W., Segev I., Burke R. B. Electrotonic architecture of type-identified alpha-motoneurons in the cat spinal cord. J Neurophysiol. 1988 Jul;60(1):60–85. doi: 10.1152/jn.1988.60.1.60. [DOI] [PubMed] [Google Scholar]
- Gogan P., Gueritaud J. P., Tyc-Dumont S. Comparison of antidromic and orthodromic action potentials of identified motor axons in the cat's brain stem. J Physiol. 1983 Feb;335:205–220. doi: 10.1113/jphysiol.1983.sp014529. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gustafsson B., Jankowska E. Direct and indirect activation of nerve cells by electrical pulses applied extracellularly. J Physiol. 1976 Jun;258(1):33–61. doi: 10.1113/jphysiol.1976.sp011405. [DOI] [PMC free article] [PubMed] [Google Scholar]
- HODGKIN A. L., HUXLEY A. F. A quantitative description of membrane current and its application to conduction and excitation in nerve. J Physiol. 1952 Aug;117(4):500–544. doi: 10.1113/jphysiol.1952.sp004764. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hines M. L., Carnevale N. T. The NEURON simulation environment. Neural Comput. 1997 Aug 15;9(6):1179–1209. doi: 10.1162/neco.1997.9.6.1179. [DOI] [PubMed] [Google Scholar]
- Jankowska E., Roberts W. J. An electrophysiological demonstration of the axonal projections of single spinal interneurones in the cat. J Physiol. 1972 May;222(3):597–622. doi: 10.1113/jphysiol.1972.sp009817. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kellerth J. O., Berthold C. H., Conradi S. Electron microscopic studies of serially sectioned cat spinal alpha-motoneurons. III. Motoneurons innervating fast-twitch (type FR) units of the gastrocnemius muscle. J Comp Neurol. 1979 Apr 15;184(4):755–767. doi: 10.1002/cne.901840408. [DOI] [PubMed] [Google Scholar]
- Mainen Z. F., Joerges J., Huguenard J. R., Sejnowski T. J. A model of spike initiation in neocortical pyramidal neurons. Neuron. 1995 Dec;15(6):1427–1439. doi: 10.1016/0896-6273(95)90020-9. [DOI] [PubMed] [Google Scholar]
- Nowak L. G., Bullier J. Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. I. Evidence from chronaxie measurements. Exp Brain Res. 1998 Feb;118(4):477–488. doi: 10.1007/s002210050304. [DOI] [PubMed] [Google Scholar]
- Nowak L. G., Bullier J. Axons, but not cell bodies, are activated by electrical stimulation in cortical gray matter. II. Evidence from selective inactivation of cell bodies and axon initial segments. Exp Brain Res. 1998 Feb;118(4):489–500. doi: 10.1007/s002210050305. [DOI] [PubMed] [Google Scholar]
- Rall W., Burke R. E., Holmes W. R., Jack J. J., Redman S. J., Segev I. Matching dendritic neuron models to experimental data. Physiol Rev. 1992 Oct;72(4 Suppl):S159–S186. doi: 10.1152/physrev.1992.72.suppl_4.S159. [DOI] [PubMed] [Google Scholar]
- Ranck J. B., Jr Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res. 1975 Nov 21;98(3):417–440. doi: 10.1016/0006-8993(75)90364-9. [DOI] [PubMed] [Google Scholar]
- Rattay F. Analysis of the electrical excitation of CNS neurons. IEEE Trans Biomed Eng. 1998 Jun;45(6):766–772. doi: 10.1109/10.678611. [DOI] [PubMed] [Google Scholar]
- Roberts W. J., Smith D. O. Analysis of threshold currents during microstimulation of fibres in the spinal cord. Acta Physiol Scand. 1973 Nov;89(3):384–394. doi: 10.1111/j.1748-1716.1973.tb05533.x. [DOI] [PubMed] [Google Scholar]
- Schwarz J. R., Eikhof G. Na currents and action potentials in rat myelinated nerve fibres at 20 and 37 degrees C. Pflugers Arch. 1987 Aug;409(6):569–577. doi: 10.1007/BF00584655. [DOI] [PubMed] [Google Scholar]
- Segev I., Fleshman J. W., Miller J. P., Bunow B. Modeling the electrical behavior of anatomically complex neurons using a network analysis program: passive membrane. Biol Cybern. 1985;53(1):27–40. doi: 10.1007/BF00355688. [DOI] [PubMed] [Google Scholar]
- Stephanova D. I., Bostock H. A distributed-parameter model of the myelinated human motor nerve fibre: temporal and spatial distributions of electrotonic potentials and ionic currents. Biol Cybern. 1996 Jun;74(6):543–547. doi: 10.1007/BF00209425. [DOI] [PubMed] [Google Scholar]
- TASAKI I. New measurements of the capacity and the resistance of the myelin sheath and the nodal membrane of the isolated frog nerve fiber. Am J Physiol. 1955 Jun;181(3):639–650. doi: 10.1152/ajplegacy.1955.181.3.639. [DOI] [PubMed] [Google Scholar]
- Thurbon D., Lüscher H. R., Hofstetter T., Redman S. J. Passive electrical properties of ventral horn neurons in rat spinal cord slices. J Neurophysiol. 1998 May;79(5):2485–2502. doi: 10.1152/jn.1998.79.5.2485. [DOI] [PubMed] [Google Scholar]
- Tranchina D., Nicholson C. A model for the polarization of neurons by extrinsically applied electric fields. Biophys J. 1986 Dec;50(6):1139–1156. doi: 10.1016/S0006-3495(86)83558-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Traub R. D., Jefferys J. G., Miles R., Whittington M. A., Tóth K. A branching dendritic model of a rodent CA3 pyramidal neurone. J Physiol. 1994 Nov 15;481(Pt 1):79–95. doi: 10.1113/jphysiol.1994.sp020420. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Warman E. N., Grill W. M., Durand D. Modeling the effects of electric fields on nerve fibers: determination of excitation thresholds. IEEE Trans Biomed Eng. 1992 Dec;39(12):1244–1254. doi: 10.1109/10.184700. [DOI] [PubMed] [Google Scholar]